*2.6.3 Optical coherence tomography (OCT) and OCT-angiography (OCT-A)*

OCT is a completely non-invasive, reproducible and quantifiable. It provides high-resolution images of the retinal layers, choroid, vitreous gel, and the vitreoretinal interface and has become the gold standard for diagnosis, assessment of treatment response, and follow-up up of patients with diabetic macular edema.

OCT angiography (OCTA) is a new non-invasive imaging technique that employs motion contrast imaging to high-resolution volumetric blood flow information, rapidly generating images similar to angiographic images [63, 65–67]. It provides a highly detailed view of the retinal vasculature, which allows for accurate delineation of the foveal avascular zone (FAZ) and detection of subtle microvascular abnormalities, including FAZ enlargement, areas of capillary non-perfusion, and intraretinal cystic spaces [66]. The possibility of detecting microvascular changes in diabetic eyes before the presence of visible microaneurysms may have important implications in the future. In this sense, OCTA could be able to quickly identify subjects at risk of DM (**Figures 6** and **7**).

### **2.7 Treatment**

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

**258**

**Figure 4.**

**Figure 3.**

*Ophthalmology Department).*

*2.6.2 Fluorescein angiography*

*Incipient PDR: large ischemic area situated temporally to the macular region, with hard exudates, dots hemorrhages, venous loops, IRMA and intraretinal neovessels; in the mid periphery, pigmented lesions post laser photocoagulation (Dr Ana Dascalu's private collection, Emergency University Hospital Bucharest,* 

*Retinophotography: Severe NPRD: multiple dot and blot hemorrhages, hard exudates, cotton wool spots (blue arrows), macular edema, VB (green arrow) and IRMA (black arrows) (Dr. Daniela Stana's private* 

*collection, Emergency University Hospital Bucharest, Ophthalmology Department, PhD thesis).*

Fluorescein angiography is an invasive, costly, and time-consuming technique but is a sensitive method to detect vascular changes due to rupture of the inner and outer blood retinal barrier in the course of DR [63, 65, 66]. The retinal vasculature is visualized with great accuracy: the examiner may identify tiny microaneurysms and differentiate between microaneurysms (hyperfluorescent) and punctiform hemorrhage (hypofluorescence by masking effect). It is an indispensable

### *2.7.1 Primary prevention*

Follow-up of patients with DR involves the ophthalmologist and the diabetologist. Extensive studies in large groups of diabetic patients have shown the beneficial role of strict control of blood glucose, hypertension and dyslipidemia in both

#### **Figure 5.**

*Fluorescein Angiography: Severe NPRD: numerous microaneurysms (hyperfluorescent dots), areas of nonperfusion (hypofluorescent, blue arrows), venous loops and IRMA, with diffuse leakage (hyperfluorescent, red arrow) (Dr Daniela Stana's private collection, PhD Thesis, Emergency University Hospital Bucharest, Ophthalmology Department).*

#### **Figure 6.**

*Optical coherence tomography (OCT) macular change analysis (before and 1 month after intravitreal anti = VEGF): hard exudates intraretinal edema with disorganization of the normal foveal architecture; macular and paramacular temporal edema decreases in area and height (Dr. Ana Dascalu's private collection, Emergency University Hospital Bucharest, Ophthalmology Department).*

#### **Figure 7.**

*OCT-A: (a) enlargement of FAZ and perifoveolar area of microvascular abnormalities; (b) mild FAZ enlargement, multiple microaneurysms (Dr. Daniela Stana's private collection, PhD Thesis, Emergency University Hospital Bucharest, Ophthalmological Department).*

**261**

*Microvascular Complications of Diabetes Mellitus: Focus on Diabetic Retinopathy (DR)…*

preventing and slowing the progression of DR. DCCT and UKPDS showed the importance of a good glycemic control in preventing microvascular damage in diabetes [68, 69]. Furthermore, every decrease with 10 mm Hg of systolic blood pressure is associated with a reduction of 35% in the risk of DR progression and of 50% in the risk of blindness [69]. Maintaining HbA1c below 7.0% (53 mmol/mol) and a systolic blood pressure below 140 mmHg is considered a realistic therapeutic target in clinical practice. Currently, the recommended serum lipid levels in DM are an optimal LDL cholesterol concentration of <100 mg/dl and desirable triglycerides

DR remains clinically silent, a long period of time until damages become irreversible. Ophthalmologic monitoring of DM subjects is essential. Frequency of screening depends on the severity of DR and the co-existence of risk factors. The follow-up schedule recommended by the ICO (International Council of Ophthalmology) Guidelines for Diabetic Eye Care is presented in **Table 2** [61].

Laser therapy has been used in DR for over 60 years and remains the mainstay of treating the ischemic retina. Applied early in severe NPDR and PDR, laser therapy leads to the prevention/regression of neovascularization and to the remission of retinal edema. Clinical studies confirm the effectiveness of laser photocoagulation by reducing vision loss by approximately 50% in patients with PDR. It is based on application of 1000-2000 laser shots, lasting 100 milliseconds, 200-250 mW of power with a size of 200-500 micrometers at the level of the middle and extreme periphery of the retina, spaced at a distance by a spot diameter, in order to destroy

Severe NPDR <3 months; Pan-retinal photocoagulation should be

Proliferative DR <1 month; Pan-retinal photocoagulation

**Therapy**

considered

considered

VEGF therapy should be considered

3-6 month; Focal laser photocoagulation should be

1-3 month; Focal laser photocoagulation/ anti-

*DOI: http://dx.doi.org/10.5772/intechopen.96548*

levels of <150 mg/dl [69–72].

*2.7.2 Retinopathy screening*

*2.7.3 Laser photocoagulation*

**DR staging Follow-up Schedule for** 

**ophthalmologists**

No apparent DR 1-2 years Observation Mild NPDR 6-12 months Observation Moderate NPDR 3-6 month Observation

Stable (Treated) PDR 6-12 months Observation

Stable DME 3-6 month Observation

*ICO Guidelines for Diabetic Eye Care: screening and follow-up schedule for diabetic retinopathy.*

**management by ophthalmologists**

**Follow-up Schedule for** 

*2.7.3.1 Classical laser*

**Diabetic Macular Edema severity**

Noncentral-involved

Central-involved

DME

DME

**Table 2.**

*Microvascular Complications of Diabetes Mellitus: Focus on Diabetic Retinopathy (DR)… DOI: http://dx.doi.org/10.5772/intechopen.96548*

preventing and slowing the progression of DR. DCCT and UKPDS showed the importance of a good glycemic control in preventing microvascular damage in diabetes [68, 69]. Furthermore, every decrease with 10 mm Hg of systolic blood pressure is associated with a reduction of 35% in the risk of DR progression and of 50% in the risk of blindness [69]. Maintaining HbA1c below 7.0% (53 mmol/mol) and a systolic blood pressure below 140 mmHg is considered a realistic therapeutic target in clinical practice. Currently, the recommended serum lipid levels in DM are an optimal LDL cholesterol concentration of <100 mg/dl and desirable triglycerides levels of <150 mg/dl [69–72].

#### *2.7.2 Retinopathy screening*

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

*Optical coherence tomography (OCT) macular change analysis (before and 1 month after intravitreal anti = VEGF): hard exudates intraretinal edema with disorganization of the normal foveal architecture; macular and paramacular temporal edema decreases in area and height (Dr. Ana Dascalu's private collection, Emergency* 

*OCT-A: (a) enlargement of FAZ and perifoveolar area of microvascular abnormalities; (b) mild FAZ enlargement, multiple microaneurysms (Dr. Daniela Stana's private collection, PhD Thesis, Emergency* 

*University Hospital Bucharest, Ophthalmology Department).*

*University Hospital Bucharest, Ophthalmological Department).*

**260**

**Figure 7.**

**Figure 6.**

DR remains clinically silent, a long period of time until damages become irreversible. Ophthalmologic monitoring of DM subjects is essential. Frequency of screening depends on the severity of DR and the co-existence of risk factors. The follow-up schedule recommended by the ICO (International Council of Ophthalmology) Guidelines for Diabetic Eye Care is presented in **Table 2** [61].

#### *2.7.3 Laser photocoagulation*

#### *2.7.3.1 Classical laser*

Laser therapy has been used in DR for over 60 years and remains the mainstay of treating the ischemic retina. Applied early in severe NPDR and PDR, laser therapy leads to the prevention/regression of neovascularization and to the remission of retinal edema. Clinical studies confirm the effectiveness of laser photocoagulation by reducing vision loss by approximately 50% in patients with PDR. It is based on application of 1000-2000 laser shots, lasting 100 milliseconds, 200-250 mW of power with a size of 200-500 micrometers at the level of the middle and extreme periphery of the retina, spaced at a distance by a spot diameter, in order to destroy


#### **Table 2.**

*ICO Guidelines for Diabetic Eye Care: screening and follow-up schedule for diabetic retinopathy.*

the VEGF-secreting ischemic retina. Immediate complications are related to eye discomfort (tingling sensation/low-intensity pain) and mild ocular inflammation (caused by retinal burns). For this reason, it is recommended to space the laser photocoagulation in 3-4 sessions. In the long run, potential complications include hemeralopia, "fan shaped" visual field changes, or even concentric narrowing of the visual field through widening of scars and subretinal fibrosis. Other less frequent side effects are membrane injury, with secondary choroidal neovascularization, damage of ciliary nerves with permanently mydriasis and loss of accommodation, uveal effusion, angle closure glaucoma, serous retinal detachment, and vitreous hemorrhage [73–75].
